Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
Authors: Qian Zhang, Daniela Matuozzo, Jérémie Le Pen, Danyel Lee, Leen Moens, Takaki Asano, Jonathan Bohlen, Zhiyong Liu, Marcela Moncada-Velez, Yasemin Kendir-Demirkol, Huie Jing, Lucy Bizien, Astrid Marchal, Hassan Abolhassani, Selket Delafontaine, Giorgia Bucciol, Laurent Abel, Hassan Abolhassani, Alessandro Aiuti, Ozge Metin Akcan, Saleh Al-Muhsen, Fahd Al-Mulla, Gulsum Alkan, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Jalila El Bakkouri, Hagit Baris Feldman, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Sefika Elmas Bozdemir, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Jamila El Baghdadi, Melike Emiroglu, Emine Hafize Erdeniz, Sara Espinosa-Padilla, Jacques Fellay, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Belgin Gulhan, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Sarah E. Henrickson, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Petr Jabandziev, Erich D. Jarvis, Timokratis Karamitros, Adem Karbuz, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, Ayse Metin, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Şadiye Kübra Tüter Öz, Tayfun Ozcelik, Qiang Pan-Hammarström, Maria Papadaki, Jean W. Pape, Aslinur Ozkaya Parlakay, Rebeca Perez de Diego, David S. Perlin, Graziano Pesole, Anna M. Planas, Petra Pokorna, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Jacques G. Rivière, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Anna Sediva, Mikko R.J. Seppänen, Mohammed Shahrooei, Anna Shcherbina, Katerina Slaba, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Lien De Somer, András N. Spaan, Ivan Tancevski, Stuart G. Tangye, Ahmad Abou Tayoun, Dimitris Thanos, Stuart E. Turvey, K M Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, François Vermeulen, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Carine Wouters, Aysun Yahsi, Saliha Kanik Yuksek, Mayana Zatz, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova, Gulsum Ical Bayhan, Sevgi Keles, Ayca Kiykim, Selda Hancerli, Filomeen Haerynck, Benoit Florkin, Nevin Hatipoglu, Tayfun Ozcelik, Guillaume Morelle, Mayana Zatz, Lisa F.P. Ng, David Chien Lye, Barnaby Edward Young, Yee-Sin Leo, Clifton L. Dalgard, Richard P. Lifton, Laurent Renia, Isabelle Meyts, Emmanuelle Jouanguy, Lennart Hammarström, Qiang Pan-Hammarström, Bertrand Boisson, Paul Bastard, Helen C. Su, Stéphanie Boisson-Dupuis, Laurent Abel, Charles M. Rice, Shen-Ying Zhang, Aurélie Cobat, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2022)

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (&amp;lt;16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5–13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10−11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.